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A number of studies had reported the association between tumor necrosis factor-alpha (TNF-α) gene polymorphisms and head and neck cancer (HNC) risk. However, the results remained controversial. Therefore, we performed a meta-analysis to derive a more precise evaluation of the association between TNF-α-308G/A polymorphism and overall HNC risk and evaluated influence of cancer types and ethnicities.A systematic literature search was performed using Pubmed, Embase, Cochrane Library, and Web of science. In total, we identified 15 studies including 2005 cancer cases and 2876 controls to evaluate the association of TNF-α-308G/A polymorphism with risk for HNC.Overall, there was no significant association between TNF-α-308G/A polymorphism and the risk of HNC. Furthermore, subgroup analyses were performed according to the types of tumor and the ethnicities, we also found there was no significant association between TNF-α-308G/A polymorphism and the risk of NPC and OC, and European and Asian populations had no statistically significant difference in the relationship of TNF-α-308G/A polymorphism and HNC susceptibility.This meta-analysis indicates that the TNF-α-308G/A polymorphism is not associated with HNC risk. In the future, large and well-designed case-control studies are needed to validate our findings.